The purpose of the proposed research is to develop methods to treat infants and children who have defects of each of the five enzymes required for urea synthesis. To achieve this goal it is planned to study alternative pathways of waste nitrogen excretion either as urea cycle intermediates or as amino acid acylation products. Other aspects of this proposal include a study of the physiological consequence of (1) heterozygosity for ornithine transcarbamylase deficiency, (2) transient asymptomatic hyperammonemia of low birth weight infants, and (3) arginine deficiency. Infants with partial or complete deficiency of carbamyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase, identified here or elsewhere, will be maintained on a low-protein regimen in which essential amino acids supplemented with arginine and/or sodium benzoate (the proportions of which depend upon the enzyme deficiency). Children who can be maintained in a stable condition using these dietary supplements will be brought to Johns Hopkins for study of enhanced waste nitrogen excretion. Premature infants will be studied in terms of physical and mental development habituation, discrimination and attention while hyperammonemia is controlled by dietary means.